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Point mutations in the mdr1 promoter of human osteosarcomas are associated with in vitro responsiveness to multidrug resistance relevated drugs

Item Type:Article
Title:Point mutations in the mdr1 promoter of human osteosarcomas are associated with in vitro responsiveness to multidrug resistance relevated drugs
Creators Name:Stein, U. and Walther, W. and Wunderlich, V.
Abstract:Among human sarcomas, osteosarcomas usually display high intrinsic mdr1 expression while malignant fibrous histiocytomas (MFH) do not. A comparative polymerase chain reaction (PCR)-based sequence analysis of the mdr1 promoter revealed point mutations in seven out of nine osteosarcomas at nucleotides +103 (2 cases T-->C) and +137 (5 cases G-->T). No changes were seen in eight MFHs. When COS cells transfected with CAT constructs containing the T-->C chloramphenicol acetyltransferase mutant mdr1 promoters were treated with vincristine or doxorubicin, expression of the CAT gene was enhanced to a higher extent than with constructs containing wild-type or G-->T-mutant mdr1 promoters. We suggest that there is a correlation between the type of mdr1 promoter mutation and responsiveness to MDR relevant drugs.
Keywords:Sarcomas, Multidrug Resistance, mdr1 Gene, Promoter, Mutation
Source:European Journal of Cancer
ISSN:0959-8049
Publisher:Pergamon Press (U.K.)
Volume:30A
Number:10
Page Range:1541-1545
Date:1994
Official Publication:https://doi.org/10.1016/0959-8049(94)00287-F
PubMed:View item in PubMed

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